Childhood hyperkinesis (extreme hyperactivity with an inability to maintain goal directed behavior) is a significant clinical problem for which there is no adequate understanding of the underlying etiology. Further, while the administration of amphetamine is the main mode of treatment, there is no physiological explanation as to why this stimulant is effective in reducing hyperactivity in hyperkinetic children. This proposal presents a new physiological model of hyperkinesis, one which accounts for the therapeutic value of amphetamines and certain other agents, and which is amenable to experimental testing. Briefly, hyperkinesis is proposed to result from subcortical seizure foci in portions of the extra-pyramidal motor system which control general activity levels. This heightened neural excitability is reversed by d-amphetamine and by other drugs which potentiate catecholamine activity in these brain regions. This model will be tested in a series of three studies; (a) induction of the hyperkinetic syndrome in preadult rats by subcortical implantation of seizure producing agents, (b) correlate the subcortical EEG seizure activity with hyperactivity levels,and (c) reverse the hyperkinesis with d-amphetamine (as well as testing other potentially beneficial agents). The present neuropsychopharmacological model of childhood hyperkinesis provides a rationale and method for the development of more effective pharmacological means for treatment and control of hyperkinetic syndromes.